Prabhu M P, Hegde M J
Department of Studies in Biosciences, Mangalore University, India.
Mutagenesis. 1991 Nov;6(6):533-6. doi: 10.1093/mutage/6.6.533.
Aneuploidies are the most common chromosomal causes for spontaneous abortions and constitute a major part of genetic disorders among the neonates. Aneuploidy producing agents (aneugens) pose serious genetic hazards to the human population. Therefore, testing for aneuploidy induction should be part of the requirement in drug safety guidelines. The aneugenic potential of pilocarpine nitrate, an alkaloid drug used as an ophthalmic solution was screened by chromosome analysis studies in the bone marrow cells of mice. Using the technique developed by Miller and Adler (1989) we evaluated changes in the mitotic index (MI), induction of chromatid contraction and spreading (C-mitoses) and decrease of anaphase frequencies as indicators of the aneuploidy inducing potency of the drug. Concentrations of pilocarpine nitrate of 4, 8 and 12 mg/kg body weight were administered intraperitoneally to mice. Colchicine-treated and water-treated animals formed the positive and negative controls. The data obtained in the cytogenetic analysis of both dose-response and time-response studies showed a significant induction of C-mitotic effects in the mouse bone marrow. The positive results indicated that the drug is a potential aneugen and should be further evaluated.
非整倍体是自然流产最常见的染色体原因，也是新生儿遗传疾病的主要组成部分。产生非整倍体的物质（非整倍体诱导剂）对人类构成严重的遗传危害。因此，检测非整倍体诱导应成为药物安全指南要求的一部分。通过对小鼠骨髓细胞进行染色体分析研究，筛选了用作眼药水的生物碱药物硝酸毛果芸香碱的非整倍体诱导潜力。我们采用Miller和Adler（1989年）开发的技术，评估有丝分裂指数（MI）的变化、染色单体收缩和分散（C-有丝分裂）的诱导以及后期频率的降低，作为该药物非整倍体诱导能力的指标。将4、8和12mg/kg体重的硝酸毛果芸香碱腹腔注射给小鼠。秋水仙碱处理组和水处理组动物分别作为阳性和阴性对照。剂量反应和时间反应研究的细胞遗传学分析数据显示，小鼠骨髓中C-有丝分裂效应有显著诱导。阳性结果表明该药物是一种潜在的非整倍体诱导剂，应进一步评估。
